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Liposomes as Drug Carriers to Liver Macrophages: Fundamental and Therapeutic Aspects

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Targeting of Drugs With Synthetic Systems

Part of the book series: NATO ASI Series ((NSSA,volume 113))

Abstract

It is well established that after intravenous injection large-size liposomes are rapidly cleared from the blood and taken up by cells belonging to the reticulo-endothelial system (RES). Particularly, fixed macrophages in liver (Kupffer cells) and spleen are actively involved in the uptake of the vesicles.1–5 Uptake occurs by way of endocytosis followed by intralysosomal degradation of liposomal lipids and release of entrapped substances.5 The natural affinity of liposomes for macrophages has been exploited in the application of liposomes as a drug delivery system to this cell type. For example, liposomes have been used as carriers of antimicrobial agents in the treatment of intracellular infections such as experiental leishmaniasis,6 candidiasis7,8 or listeriosis.9 In these infections the microorganisms are lodged in the lysosomes of tissue macrophages, precisely the site where the liposomes end up after intravenous injection. Thus, encapsulation of relevant antibiotic drugs within liposomes results in an increased therapeutic index of these drugs when administered intravenously.

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References

  1. F.H. Roerdink, E. Wisse, H.W.M. Morselt, J. Van der Meulen and G.L. Scherphof, Cellular distribution of intravenously injected protein-containing liposomes in the rat liver, in: “Kupffer cells and other liver sinusoidal cells,” E. Wisse and D. Knook, Eds., Elsevier/North-Holland, Amsterdam (1977).

    Google Scholar 

  2. F. Roerdink, J. Dijkstra, G. Hartman, B. Bolscher and G. Scherphof, The involvement of parenchymal, Kupffer and endothelial liver cells in hepatic uptake of intravenously injected liposomes. Effects of lanthanum and gadolinium salts, Biochim. Biophys. Acta 677:79 (1981).

    Article  CAS  Google Scholar 

  3. G. Poste, C. Bucana, A. Raz, P. Bugelski, R. Kirsh and I.J. Fidler, Analysis of the fate of systemically administered liposomes and implications for their use in drug delivery, Cancer Res. 42:1412 (1982).

    CAS  Google Scholar 

  4. Y.E. Rahman, E.A. Cerny, K.R. Patel, E.H. Lau and B.J. Wright, Differential uptake of liposomes varying in size and lipid composition by parenchymal and Kupffer cells of mouse liver, Life Sci. 31:2061 (1982).

    Article  CAS  Google Scholar 

  5. G. Scherphof, F. Roerdink, J. Dijkstra, H. Ellens, R. de Zanger and E. Wisse, Uptake of liposomes by rat and mouse hepatocytes and Kupffer cells, Biol. Cell 47:47 (1981).

    Google Scholar 

  6. C.R. Alving, E.A. Steck, W.L. Chapman, Jr., V.B. Waits, L.D. Hendricks, G.M. Swartz, Jr. and W.L. Hanson, Therapy of Leishmaniasis: superior efficacies of liposome-encapsulated drugs, Proc. Natl. Acad. Sci. U.S.A. 75:2959 (1978).

    Article  CAS  Google Scholar 

  7. G. Lopez-Berestein, R. Mehta, R.L. Hopfer, K. Mills, L. Kasi, K. Mehta, V. Fainstein, M. Luna, E.M. Hersh and R. Juliano, Treatment and prophylaxis of disseminated infection due to Candida albicans in mice with liposome-encapsulated amphotericin B, J. Infect. Dis. 147:939 (1983).

    Article  CAS  Google Scholar 

  8. G. Lopez-Berestein, R.L. Hopfer, R. Mehta, K. Mehta, E.M. Hersh and R.L. Juliano, Liposome-encapsulated amphotericin B for treatment of disseminated candidiasis in neutropenic mice, J. Infect. Dis. 150:278 (1984).

    Article  CAS  Google Scholar 

  9. I.A.J.M. Bakker-Woudenberg, A.F. Lokerse, F.H. Roerdink, D. Regts and M.F. Michel, Free vs. liposome-entrapped ampicillin in the treatment of Listeria monocytogenes infection in normal mice and athymic (nude) mice, J. Infect. Dis. 151:917 (1985).

    Article  CAS  Google Scholar 

  10. G. Poste, C. Bucana and I.J. Fidler, Stimulation of host response against metastatic tumours by liposome-encapsulated immunomodulators, in: “Targeting of drugs,” G. Gregoriadis, J. Senior and A. Trouet, eds., Plenum, New York (1982).

    Google Scholar 

  11. J. Dijkstra, W.J.M. van Galen, C.E. Hulstaert, D. Kalicharan, F.H. Roerdink and G.L. Scherphof, Interaction of liposomes with Kupffer cells in vitro, Exp. Cell Res. 150:161 (1984).

    Article  CAS  Google Scholar 

  12. J. Dijkstra, M. van Galen and G.L. Scherphof, Effects of ammonium chloride and chloroquine on endocytic uptake of liposomes by Kupffer cells in vitro, Biochim. Biophys. Acta 804:58 (1984).

    Article  CAS  Google Scholar 

  13. J. Dijkstra, M. van Galen, D. Regts and G. Scherphof, Uptake and processing of liposomal phospholipids by Kupffer cells in vitro, Eur. J. Biochem. 148:391 (1985).

    Article  CAS  Google Scholar 

  14. J. Dijkstra, M. van Galen and G. Scherphof, Influence of liposome charge on the association of liposomes with Kupffer cells in vitro. Effects of divalent cations and competition with latex particles. Biochim. Biophys. Acta 813:287 (1985).

    Article  CAS  Google Scholar 

  15. J. Dijkstra, M. van Galen and G. Scherphof, Effects of (dihydro)-cytochalasin B, colchicine, monensin and trifluoperazine on uptake and processing of liposomes by Kupffer cells in culture. Biochim. Biophys. Acta 845:34 (1985).

    Article  CAS  Google Scholar 

  16. R.L. Juliano and D. Stamp, The effects of particle size and charge on the clearance rates of liposomes and liposome encapsulated drugs, Biochem. Biophys. Res. Commun. 63:651 (1975).

    Article  CAS  Google Scholar 

  17. F. Roerdink, J. Regts, B. van Leeuwen and G. Scherphof, Intrahepatic uptake and processing of intravenously injected small unilamellar phospholipid vesicles in rats, Biochim. Biophys. Acta 770:195 (1984).

    Article  CAS  Google Scholar 

  18. H.H. Spanjer, Targeting of liposomes to liver cells in vivo, Ph.D. Thesis, State University Groningen, 1985.

    Google Scholar 

  19. G. Gregoriadis and J. Senior, The phospholipid component of small unilamellar liposomes controls the rate of clearance of entrapped solutes from the circulation, FEBS Lett. 119:43 (1980).

    Article  CAS  Google Scholar 

  20. P.-S. Wu, G.W. Tin and J.D. Baldeschwieler, Phagocytosis of carbohydrate-modified phospholipid vesicles by macrophage, Proc. Natl. Acad. Sci. U.S.A. 78:2033 (1981).

    Article  CAS  Google Scholar 

  21. R.A. Schwendener, P.A. Lagocki and Y.E. Rahman, The effects of charge and size on the interaction of unilamellar liposomes with macrophages, Biochim. Biophys. Acta 772:93 (1984).

    Article  CAS  Google Scholar 

  22. J.D. Baldeschwieler, Phospholipid vesicle targeting using synthetic glycolipid and other determinants, Ann. N.Y. Acad. Sci. U.S.A. 446:349 (1985).

    Article  CAS  Google Scholar 

  23. J.C. Wilschut, J. Regts, H. Westenberg and G. Scherphof, Hydrolysis of phosphatidylcholine liposomes by phospholipases A2, Effects of the local anaesthetic dibucaine. Biochim. Biophys. Acta 433:20 (1976).

    Article  CAS  Google Scholar 

  24. R.E. Niemann and B. Lorder, Listeriosis in adults: a changing pattern. Report of eight cases and review of the literature, Rev. Inf. Dis. 2:207 (1980).

    Article  Google Scholar 

  25. G. Lopez-Berestein, V. Fainstein, R. Hopfer, K. Mehta, M.P. Sullivan, M. Keating, M.G. Rosenblum, R. Mehta, M. Luna, E.M. Hersh, J. Reuben, R.L. Juliano and G.P. Bodey, Liposomal amphotericin B for the treatment of systemic fungal infections in patients with cancer: a preliminary study, J. Infect. Dis. 151:704 (1985).

    Article  CAS  Google Scholar 

  26. E.S. Kleinerman, A.J. Schroit and W.E. Fogler, Tumoricidal activity of human monocytes activated in vitro by free and liposome-encapsulated human lymphokines. J. Clin. Invest. 72:304 (1983).

    Article  CAS  Google Scholar 

  27. L. Varesio, E. Blasi, G.B. Thurman, J.E. Talmadge, R.H. Wiltrout and R.B. Herberman, Potent activation of mouse macrophages by recombinant interferon, Cancer Res. 44:4465 (1984).

    CAS  Google Scholar 

  28. G. Lopez-Berestein, K. Mehta, R. Mehta, R.L. Juliano and E.M. Hersh, The activation of human monocytes by liposome-encapsulated muramyl dipeptide analogues, J. Immunol. 130:1500 (1983).

    CAS  Google Scholar 

  29. S. Sone and I.J. Fidler, In vitro activation of tumoricidal properties in rat alveolar macrophages by synthetic muramyl dipeptide encapsulated in liposomes. Cell. Immunol. 57:42 (1981).

    Article  CAS  Google Scholar 

  30. I.J. Fidler, Z. Barnes, W.E. Fogler, R. Kirsh, P. Bugelski and G. Poste, Involvement of macrophages in the eradication of established metastases following intravenous injection of liposomes containing macrophage activators, Cancer Res. 42:496 (1982).

    CAS  Google Scholar 

  31. P.S. Thombre and S.D. Deodhar, Inhibition of liver metastases in murine colon adenocarcinoma by liposomes containing human C-reactive-protein or crude lymphokine, Cancer Immunol. Immunother. 16:145 (1984).

    Article  CAS  Google Scholar 

  32. Z.L. Xu, C.D. Bucana and I.J. Fidler, In vitro activation of murine Kupffer cells by lymphokines or endotoxins to lyse syngeneic tumor cells, Am. J. Pathol. 117:372 (1984).

    CAS  Google Scholar 

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Authors and Affiliations

  1. Laboratory of Physiological Chemistry, University of Groningen, Bloemsingel 10, 9712 KZ, Groningen, The Netherlands

    Frits Roerdink, Joke Regts, Toos Daemen & Gerrit Scherphof

  2. Department of Clinical Microbiology, Erasmus University Rotterdam, P.O. Box 1738, 3000 DR, Rotterdam, The Netherlands

    Irma Bakker-Woudenberg

Authors
  1. Frits Roerdink
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  2. Joke Regts
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  3. Toos Daemen
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  4. Irma Bakker-Woudenberg
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  5. Gerrit Scherphof
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Editors and Affiliations

  1. Royal Free Hospital School of Medicine, London, England

    Gregory Gregoriadis  & Judith Senior  & 

  2. Smith Kline & French Laboratories, Philadelphia, Pennsylvania, USA

    George Poste

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© 1986 Plenum Press, New York

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Roerdink, F., Regts, J., Daemen, T., Bakker-Woudenberg, I., Scherphof, G. (1986). Liposomes as Drug Carriers to Liver Macrophages: Fundamental and Therapeutic Aspects. In: Gregoriadis, G., Senior, J., Poste, G. (eds) Targeting of Drugs With Synthetic Systems. NATO ASI Series, vol 113. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5185-6_14

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  • DOI: https://doi.org/10.1007/978-1-4684-5185-6_14

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4684-5187-0

  • Online ISBN: 978-1-4684-5185-6

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